Plain English Summary

Background and study aimsMonochorionic diamniotic (MCDA) twin pregnancy is where a woman is pregnant with twins who share a single placenta. This type of pregnancy is very high-risk, as it can result in fatal complications such as twin-twin transfusion syndrome, TTTS (a condition where blood flows unevenly between the babies). This is thought to happen because inter-twin placental anastomoses (connections between arteries and veins) can form, causing a significant change in the blood pressures of the twins as one twin "donates" a significant proportion of its blood to the other "recipient" twin. The donor twin may then go into kidney failure and produce very little amniotic fluid (fetal urine), and the recipient twin produces too much amniotic fluid and may go into heart failure. Without treatment, 90% of these pregnancies will miscarry before 26 weeks. However, there is an effective treatment for TTTS called fetoscopic laser ablation (FLA) which involves inserting a small camera into the amniotic fluid sac of the recipient twin and burning the vascular anastomoses on the surface of the placenta, to block these connections and attempt to rebalance the blood flow between the twins. In 85% cases treated by FLA at least one twin will survive, in 40% of cases 2 twins will survive. The aim of this study is to develop a model to predict which MC twin pregnancies will develop complications later in pregnancy. The project takes place in two parts, the first part looking back on women who previously had an MCDA pregnancy, and the second part looking at women who are currently experiencing a MCDA pregnancy.

Who can participate?In the first part of the study, women who had MCDA pregnancies and had samples of blood and information about the result of their pregnancy stored. In the second part of the study, women aged 18-50 who book at Birmingham Women's Hospital with MC twin pregnancies (cohort C) and those who are referred to Birmingham Women's Hospital for assessment of treatment of complications of MC twin pregnancies (cohort S) can participate.

What does the study involve?In the first part of the study, the researchers look at any chemical indicators (biomarkers) of angiogenesis (new blood vessel formation) and the function of the placenta in previously stored blood samples that were taken in the first 12 weeks of pregnancy. These are then compared to information taken from ultrasound measurements at the same time and then matched to the outcomes (how the pregnancy progressed). In the second part of the study, there are two groups of women being examined: Cohort S and Cohort C. Women in both groups have blood samples taken at 12, 16 and 20 weeks of their pregnancy. In addition, their ultrasound results and information about the outcome of the pregnancy is also collected. For participants in cohort C (women booked to have FLA), a sample of blood and amniotic fluid, and ultrasound measurements are also taken immediately before and after they have the FLA procedure. These blood samples are then looked at in the lab to look for noteworthy biomarkers.

What are the possible benefits and risks of participating?There are no direct benefits involved with taking part in the study. In the second study, there is a small risk that participants may experience pain, discomfort or bruising during or after blood samples are taken.

Where is the study run from?Birmingham Women's Hospital (UK)

When is the study starting and how long is it expected to run for?October 2014 to October 2018

Who is funding the study?1. The Richard and Jack Wiseman Trust (UK)2. British Maternal and Fetal Medicine Society (UK)

Intervention

There are two parts to this trial: a retrospective study and a prospective study.

In the retrospective study (OMMIT 1), markers of angiogenesis (blood vessel developmental) and placental function in the stored first-trimester blood samples will be analysed, these will then be combined with first-trimester ultrasound measurements and matched to outcome data to attempt to create a model.

In the prospective study (OMMIT 2), there will be 2 cohorts: Cohort S and Cohort C.Cohort S will have blood samples taken at 12, 16 and 20 weeks gestation, their ultrasound measurements will be recorded and their outcomes collected. Cohort C will have a maternal blood sample pre- FLA and post-FLA. Amniotic fluid samples will be collected immediately pre-FLA and post-FLA, and ultrasound measurements. Researchers will use the results of the retrospective study to decide which biomarkers to investigate in the blood and amniotic fluid samples.The following will then be compared:1. "Normal" Cohort S blood samples to Cohort C samples2. Cohort S samples longitudinally over the 3 time points3. Cohort C pre-FLA and post-FLA blood and amniotic fluid samples